Characterization of Hemagglutinin Negative Botulinum Progenitor Toxins
Botulism is a disease involving intoxication with botulinum neurotoxins (BoNTs), toxic proteins produced by Clostridium botulinum and other clostridia. The 150 kDa neurotoxin is produced in conjunction with other proteins to form the botulinum progenitor toxin complex (PTC), alternating in size from...
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| Format: | Article |
| Language: | English |
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MDPI AG
2017-06-01
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| Series: | Toxins |
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| Online Access: | http://www.mdpi.com/2072-6651/9/6/193 |
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| author | Suzanne R. Kalb Jakub Baudys Theresa J. Smith Leonard A. Smith John R. Barr |
| author_facet | Suzanne R. Kalb Jakub Baudys Theresa J. Smith Leonard A. Smith John R. Barr |
| author_sort | Suzanne R. Kalb |
| collection | DOAJ |
| description | Botulism is a disease involving intoxication with botulinum neurotoxins (BoNTs), toxic proteins produced by Clostridium botulinum and other clostridia. The 150 kDa neurotoxin is produced in conjunction with other proteins to form the botulinum progenitor toxin complex (PTC), alternating in size from 300 kDa to 500 kDa. These progenitor complexes can be classified into hemagglutinin positive or hemagglutinin negative, depending on the ability of some of the neurotoxin-associated proteins (NAPs) to cause hemagglutination. The hemagglutinin positive progenitor toxin complex consists of BoNT, nontoxic non-hemagglutinin (NTNH), and three hemagglutinin proteins; HA-70, HA-33, and HA-17. Hemagglutinin negative progenitor toxin complexes contain BoNT and NTNH as the minimally functional PTC (M-PTC), but not the three hemagglutinin proteins. Interestingly, the genome of hemagglutinin negative progenitor toxin complexes comprises open reading frames (orfs) which encode for three proteins, but the existence of these proteins has not yet been extensively demonstrated. In this work, we demonstrate that these three proteins exist and form part of the PTC for hemagglutinin negative complexes. Several hemagglutinin negative strains producing BoNT/A, /E, and /F were found to contain the three open reading frame proteins. Additionally, several BoNT/A-containing bivalent strains were examined, and NAPs from both genes, including the open reading frame proteins, were associated with BoNT/A. The open reading frame encoded proteins are more easily removed from the botulinum complex than the hemagglutinin proteins, but are present in several BoNT/A and /F toxin preparations. These are not easily removed from the BoNT/E complex, however, and are present even in commercially-available purified BoNT/E complex. |
| first_indexed | 2024-12-10T07:54:36Z |
| format | Article |
| id | doaj.art-15eb3dee1869411db240e3c64b816e40 |
| institution | Directory Open Access Journal |
| issn | 2072-6651 |
| language | English |
| last_indexed | 2024-12-10T07:54:36Z |
| publishDate | 2017-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Toxins |
| spelling | doaj.art-15eb3dee1869411db240e3c64b816e402022-12-22T01:56:56ZengMDPI AGToxins2072-66512017-06-019619310.3390/toxins9060193toxins9060193Characterization of Hemagglutinin Negative Botulinum Progenitor ToxinsSuzanne R. Kalb0Jakub Baudys1Theresa J. Smith2Leonard A. Smith3John R. Barr4Centers for Disease Control and Prevention, National Center for Environmental Health, Division of Laboratory Sciences, 4770 Buford Hwy, NE, Atlanta, GA 30341, USACenters for Disease Control and Prevention, National Center for Environmental Health, Division of Laboratory Sciences, 4770 Buford Hwy, NE, Atlanta, GA 30341, USAMolecular and Translational Sciences Division, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Ft. Detrick, MD 21702, USAOffice of the Chief Scientist, Medical Research and Materiel Command (MRMC), Fort Detrick, MD 21702, USACenters for Disease Control and Prevention, National Center for Environmental Health, Division of Laboratory Sciences, 4770 Buford Hwy, NE, Atlanta, GA 30341, USABotulism is a disease involving intoxication with botulinum neurotoxins (BoNTs), toxic proteins produced by Clostridium botulinum and other clostridia. The 150 kDa neurotoxin is produced in conjunction with other proteins to form the botulinum progenitor toxin complex (PTC), alternating in size from 300 kDa to 500 kDa. These progenitor complexes can be classified into hemagglutinin positive or hemagglutinin negative, depending on the ability of some of the neurotoxin-associated proteins (NAPs) to cause hemagglutination. The hemagglutinin positive progenitor toxin complex consists of BoNT, nontoxic non-hemagglutinin (NTNH), and three hemagglutinin proteins; HA-70, HA-33, and HA-17. Hemagglutinin negative progenitor toxin complexes contain BoNT and NTNH as the minimally functional PTC (M-PTC), but not the three hemagglutinin proteins. Interestingly, the genome of hemagglutinin negative progenitor toxin complexes comprises open reading frames (orfs) which encode for three proteins, but the existence of these proteins has not yet been extensively demonstrated. In this work, we demonstrate that these three proteins exist and form part of the PTC for hemagglutinin negative complexes. Several hemagglutinin negative strains producing BoNT/A, /E, and /F were found to contain the three open reading frame proteins. Additionally, several BoNT/A-containing bivalent strains were examined, and NAPs from both genes, including the open reading frame proteins, were associated with BoNT/A. The open reading frame encoded proteins are more easily removed from the botulinum complex than the hemagglutinin proteins, but are present in several BoNT/A and /F toxin preparations. These are not easily removed from the BoNT/E complex, however, and are present even in commercially-available purified BoNT/E complex.http://www.mdpi.com/2072-6651/9/6/193botulinum neurotoxinbotulismprotein toxintoxin complexproteomics |
| spellingShingle | Suzanne R. Kalb Jakub Baudys Theresa J. Smith Leonard A. Smith John R. Barr Characterization of Hemagglutinin Negative Botulinum Progenitor Toxins Toxins botulinum neurotoxin botulism protein toxin toxin complex proteomics |
| title | Characterization of Hemagglutinin Negative Botulinum Progenitor Toxins |
| title_full | Characterization of Hemagglutinin Negative Botulinum Progenitor Toxins |
| title_fullStr | Characterization of Hemagglutinin Negative Botulinum Progenitor Toxins |
| title_full_unstemmed | Characterization of Hemagglutinin Negative Botulinum Progenitor Toxins |
| title_short | Characterization of Hemagglutinin Negative Botulinum Progenitor Toxins |
| title_sort | characterization of hemagglutinin negative botulinum progenitor toxins |
| topic | botulinum neurotoxin botulism protein toxin toxin complex proteomics |
| url | http://www.mdpi.com/2072-6651/9/6/193 |
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